​An elderly diabetic man presents to hospital with a fever, tachycardia and hypotension. He is septic and so blood cultures are taken and he is started on IV Piptazobactam as per the hospitals empirical guidelines for sepsis. There is no obvious focus and therefore source control (e.g. draining of an abscess) at this time is not possible.

The next day his blood cultures signal positive and a beta-haemolytic streptococcus is isolated. What does this mean? What is the significance?

Does the terminology around beta-haemolytic streptococci confuse you? It did me when I was a student and junior doctor; I couldn’t understand why beta-haemolytic streptococcus wasn’t the Group B streptococcus! They both have a “B” in them just one is the Latin letter while the other is Greek; surely they are the same thing? Well no, they’re not so how did I eventually get to grips with them.

What does beta-haemolytic mean?Beta-haemolytic is a laboratory term that has escaped into the clinical terminology; it’s got nothing to do with whether your patient is on a haematology ward or in an “early stage of testing” to see if they are bleeding profusely from somewhere! So where does it come from? In the microbiology laboratory bacteria are often plated out on agar containing sheep’s blood, blood agar, it used to be human blood but this has gone out of fashion. Where streptococci are concerned there are three types of breakdown or haemolysis of red blood cells (RBC) between the bacteria and the sheep’s blood in the agar. The important point is that the type of haemolysis is a laboratory description of what happens on blood agar and nothing else:

Alpha-haemolytic = partial breakdown of RBC giving a green discolouration, these are often known as Viridans streptococci as the Latin for green is “viride”

Beta-haemolytic = complete breakdown of RBC to the point where the agar goes clear and you can “beta (better) see through it”!

Non-haemolytic = there is no breakdown of RBC, in old text books this is called gamma-haemolysis, Gamma is the third letter of the Greek alphabet akin to “C” but this is a rubbish term as there is no haemolysis

​Being able to distinguish between the types of bacteria allows the laboratory to begin the process of identifying the bacterium, which ultimately allows us to distinguish the clinical significance of the microorganism and decide how best to treat it. For an alpha-haemolytic streptococcus isolated in a blood culture this would involve investigations and treatment for possible infective endocarditis whereas for non-haemolytic streptococci, the bowel is the most likely site of origin and treatment and investigations can be targeted to this area of the body.

Beta-haemolytic streptococci come in Groups?! But what does the letter mean?The letter before the laboratory description, e.g. “Group A or Group B etc.”, refers to a molecule or antigen on the bacterial cell wall. It was first discovered in 1933 by Rebecca Lancefield, an American Microbiologist born in 1895, and became known as Lancefield grouping. Lancefield grouping only applies to Beta-haemolytic streptococci. Do not group the alpha or non-haemolytic streptococci; in these bacteria the grouping antigens may lead to a misidentification (and false significance) of the microorganism e.g. a non-haemolytic streptococcus that groups with an “A” is not S. pyogenes and does not have the same significance as S. pyogenes. If you do this you will end up mismanaging patients! Take my word for it… don’t group alpha and non-haemolytic streptococci… just don’t do it, it’s wrong!

There are 6 main Lancefield groups of beta-haemolytic streptococci: A, B, C, D, F and G. Did you spot the missing “E”? Group E is a beta-haemolytic streptococcus sometimes found in milk which is non-pathogenic to humans. The grouping system actually goes all the way from A to S, but they are non-pathogenic to humans from H to S.

To add to the confusion, within each of the 6 groups of pathogenic beta-haemolytic streptococci there can be one or more types of bacterium. To help, their specific names can give some idea of the types of infection they cause (although not all):

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​Okay, we’re getting there… honest. Stick with it. We have laboratory terms and the groups so now we need to consider the clinical relevance of all these groups.

Breaking the lists down furtherMy next step to help me understand the clinical relevance of the beta-haemolytic streptococci is to break the above list in half; I find shorter lists easier to remember.

I consider groups A, C and G together because they cause the same types of infections in humans: cellulitis, tonsillitis, septic arthritis and osteomyelitis. They are isolated from the same types of specimens; skin swabs, throat swabs, synovial fluid and bone.

The Group A beta-haemolytic streptococcus comes with an extra health warning in that it is the most common cause of the life-threatening skin and soft tissue infection necrotising fasciitis. If Group A is isolated in one of your patient’s samples from a normally sterile site e.g. an abscess, joint fluid, blood culture, contact a Microbiologist immediately.

I then consider groups B, D and F together because they are all part of the normal flora of the gastrointestinal tract: the bowel. When these bacteria are found in blood cultures then the important question to ask is how did they get there from the gut? Often there is undiagnosed bowel pathology such as cancer.

The Group B beta-haemolytic streptococcus also comes with an extra health warning in that it is a common cause of neonatal sepsis which requires treatment with IV Benzylpenicillin and Gentamicin. Babies are exposed to it during normal vaginal deliveries; Group B beta-haemolytic streptococcus is part of the normal genital flora of up to 40% of pregnant women see blog about screening for Group B streptococcus in pregnancy. Babies become colonised at birth (Group B beta-haemolytic streptococcus becomes a major part of their normal flora), so when or if an infection occurs it is likely to be the causative bacterium.

Putting it all togetherSo now we can combine the descriptive appearance, the Lancefield group, the bacterial name, site of normal flora and the significance of finding these bacteria in clinical specimens. The reason for going to all this trouble is to be able to decide if the beta-haemolytic streptococcus you have isolated is causing an infection or just colonising AND if it is found in a normally sterile site, where did it come from? The table below combines the information about group, name, site of normal flora and clinical significance and can be used to answer these questions.

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​Examples of how to interpret cultures of beta-haemolytic streptococciIf a throat swab grows a Group A beta-haemolytic streptococcus then the bacterium is a known common cause of tonsillitis but if a Group D beta-haemolytic streptococcus grows instead it is a colonising bacteria and part of the patients upper gastrointestinal flora at that time (Yep you can have the same bacteria in your bottom as well as your mouth. Nice hey!)

If a Group B beta-haemolytic streptococcus was found on a vaginal swab, it would be considered normal flora. However, if a blood culture from an elderly woman grows a Group B beta-haemolytic streptococcus then the patient should have an echocardiography to look for infective endocarditis and investigations to look for an underlying pelvic malignancy (even if there are no other symptoms of this).

So this is how I came to grips with the beta-haemolytic streptococci. They are complicated and you may need to work through this blog a few times before you are happy with them yourself. Don’t worry, this is normal… just stick with it….

For our patient above, the beta-haemolytic streptococcus grouped as a G prompting further questioning which revealed a painful knee and underlining septic arthritis. The Microbiologist also alerted the junior to the possible association of Group G and bowel cancer; the patient underwent investigation of his bowel and an early stage bowel cancer was found and removed through surgery. Understanding the beta-haemolytic streptococci was instrumental in helping this patient both in the short term of treating his sepsis but also diagnosing an unknown problem of bowel cancer.

PS You have to admit “discombobulated” is a great word!

Abdelhalim Yousef

11/12/2016 07:19:22 am

Hi
Where is S bovis?
Thanx

David Garner

11/12/2016 06:41:12 pm

Hi Abdelhalim
S. bovis doesn't appear because it is not a Beta-haemolytic streptococcus. It is another great example of why non-haemolytic streptococci should not be grouped as I have seen these group with B or D and even both at the same time which is really misleading.
Thanks for the question.

Abdelhalim Yousef

12/12/2016 07:12:11 am

Thank you for your concern. Someone (not me of course) could say:

1-Is there a relation between the streptolysins and the typing of the capsule?

2-Enterococci could be a or non hemolytic (also, S agalactiae is non-hemolytic) so we might miss them!

3-S bovis is a group D, so it would not been typed all the time!

Sorry, for making the issue more discombobulated!
Best regards

David Garner

12/12/2016 03:52:51 pm

Thank you for the comment. The issue is not whether alpha or non-haemolytic streptococci might test positive to a particular group. Lancefield grouping is not a method for identifying alpha or non-haemolytic streptococci. Another method should be used to identify alpha and non-haemolytic streptococci e.g. biochemical reactions such as APIs, MaldiTOF, PCR. If a streptococcus is beta-haemolytic it can be grouped, if it is not beta-haemolytic it should be identified using a different method. I'm not saying don't identify streptococci, just only use Lancefield grouping if they are beta-haemolytic.